A non-Jewish, obligate Tay-Sachs disease (TSD) heterozygote is healthy, yet expresses no hexosaminidase A (hex A) in some tissues and only about 15-25% of the control levels of hex A in other tissues, including cultured skin fibroblasts. The enzymatic response is the same for authentic and synthetic substrates. Cultured skin fibroblasts provide the enzyme source for the studies of the variant (and only) hex A catalytically active in this doubly heterozygous individual. The variant hex A is relatively heat-stable and is heat-activated under assay conditions. The biological and biochemical properties of hex A and heat-stable hex B are being compared with those derived from cultured skin fibroblasts of a control and an age- and sex-matched obligate TSD carrier. Fibroblast studies include pH optimum, Vmax and Km values of several synthetic substrates, Ki for competitive (lactone) and non-competitive inhibitors, molecular weight, affinity for concanavalin A, uptake by hexosaminidase-deficient fibroblasts, and secretion of hexosaminidase A into the medium. The lymphocytes of the variant carrier will be studied after phytohemagglutinin stimulation. Several tissues, including some without hex A, will be studied immunologically with antibodies made to purified placental hex A.